Olanzapine intramuscular shows better efficacy than zuclopenthixol acetate intramuscular in reducing the need for restraint, but not in comparison to haloperidol intramuscular.

Many psychotic patients are treated with antipsychotic medications during acute agitation and aggressive behavior episodes in an attempt to achieve a rapid calming effect. Those medications include olanzapine, zuclopenthixol acetate, and haloperidol intramuscular administration. This study compared the effectiveness of these injections in reducing the need for restraint during agitated-psychotic episodes that include aggression. Sociodemographical and clinical data were retrieved from the electronic medical records of 179 patients who needed rapid calming while hospitalized in a mental health center with acute psychosis. The treatments administered were olanzapine intramuscular, zuclopenthixol acetate intramuscular, and haloperidol intramuscular. The assessed outcomes were rate of restraint and violent behavior. Olanzapine was found significantly more effective in reducing the need for restraint compared to zuclopenthixol acetate. No significant differences were found between haloperidol and the other two with regard to restraint. Neither were other significant differences found between the groups with regard to violent or self-harming behaviors. No significant differences were found in the rate of violent behavior and antipsychotic dosage at discharge. In conclusion, in inpatients with acute agitated psychosis, olanzapine intramuscular shows better efficacy in reducing the need for restraint, at least as compared to zuclopenthixol acetate intramuscular.

Eficácia, segurança e efetividade comparada de palmitato de paliperidona e outros antipsicóticos injetáveis de efeito prolongado para tratamento de esquizofrenia: revisão rápida de evidências / Efficacy, safety and effectiveness in the real world for paliperidone palmitate compared to the others long acting injectable antipsychotics for schizophrenia treatment: rapid review of evidence

Tecnologia: Palmitato de Paliperidona (PP) é um antipsicótico injetáveis de efeito prolongado (AIEP). Indicação: Tratamento sintomático da esquizofrenia. Objetivo: Comparar a eficácia, segurança e efetividade terapêutica entre PP e outros AIEP para o tratamento de esquizofrenia em adultos. Pergunta: O PP é mais eficaz e seguro que os outros AIEP (Decanoato de Haloperidol, Enantato de Flufenazina, Decanoato de Zuclopentixol, Risperidona-IEP) para o tratamento sintomático de esquizofrenia em adultos? Métodos: Levantamento bibliográfico, com estratégias estruturadas de busca, na base de dados PUBMED. Foi feita avaliação da qualidade metodológica das revisões sistemáticas (RS), ensaios clínicos randomizados (ECR) e dos estudos observacionais de efetividade no mundo real (EOEMR) com as ferramentas Assessing the Methodological Quality of Systematic Reviews (AMSTAR), Delphi List e Newcastle-Ottawa Scale (NOS), respectivamente. Resultados: Foram selecionadas 3 RS, 1 ECR e 3 EOEMR. Conclusão: PP (de aplicação mensal) tem similar eficácia e segurança com a Risperidona-IEP para o tratamento de esquizofrenia, exceto que provoca menor incidência de sintomas extrapiramidais. PP e Decanoato de Haloperidol são similares na eficácia e segurança para o tratamento de esquizofrenia, inclusive no risco de sintomas extrapiramidais (discinesias tardias e parkinsonismo), exceto que PP tem menor incidência de acatisia. PP é similar aos outros AIEP nos vários desfechos de eficácia e segurança terapêutica, inclusive mortalidade

Technology: Paliperidone palmitate (PP) is a long-acting injectable (LAI) antipsychotics. Indication: Symptomatic treatment of schizophrenia. Objective: To compare the therapeutic efficacy, safety and effectiveness in the real world between PP and other LAI antipsychotics for the treatment of schizophrenia in adults. Question: Is PP more effective and safer than other LAI antipsychotics (Haloperidol Decanoate, Fluphenazine Enanthate, Zuclopentixol Decanoate, Risperidone-LAI), for the symptomatic treatment of schizophrenia? Methods: Bibliographic survey, with structured search strategies, in the PUBMED database. Na evaluation was made of the methodological quality of systematic reviews (SR), randomized clinical trials (RCT) and observational studies (OS) of effectiveness in the real world with Assessing the Methodological Quality of Systematic Reviews (AMSTAR), Delphi List and Newcastle-Ottawa Scale (NOS) tools, respectively. Results: 3 SR, 1 RCT and 3 OE were included. Conclusion: PP (monthly dose presentation) has similar efficacy and safety with Risperidone-LAI for the treatment of schizophrenia, except that it causes a lower incidence of extrapyramidal symptoms. PP and Haloperidol Decanoate are similar in efficacy and safety for the treatment of schizophrenia, including the risk of extra-pyramidal symptoms (tardive dyskinesias and parkinsonism), except that PP has a lower incidence of akathisia. PP has similar outcomes of efficacy and safety to the other LAI antipsychotics, including mortality risk

Informe rápido de evaluación de tecnologías sanitarias: ¿Deberia usarse Zuclopenthixol vs. Haloperidol para el tratamiento de la psicosis aguda? / Quick report on evaluation of sanitary technologies: ¿Deberia use Zuclopenthixol vs. Haloperidol for the treatment of acute psychosis?

INTRODUCCIÓN Importancia del problema (Conocimiento de base mas epidemiologia o datos locales). Descripcion de la intervención/ Tecnología evaluada: Zuclopenthixol inyectable. Porque podría funcionar esta intervencion. BÚSQUEDA: Se realizó una búsqueda en Pubmed y en Cochrane Schizophrenia Group's Trials Register (ultima búsqueda 25 de Septiembre 2019). No hubo restricción de lenguaje, fecha, tipo de documento o publicación. Se realizó además una búsqueda en el repositorio de revisiones sistemáticas Epistemonikos y en Cochrane Library y en Pubmed. RESULTADOS: Un estudio multicêntrico realizado por Heikkila 1981a incluido en el perfil de evidencia sobre eficacia y seguridad de zuclopenthixol comparado con placebo (Tabla 1) realizado en Finlandia incluyo 63 pacientes con chronic schizophrenia (n = 58) u otros trastornos psicoticos (n = 5, paranoic state, depressive/PD) con una duracion de la enfermedad > 10 años n: 40 y n:11 com una duracion de la enfermedad > cinco años en el context de pacientes hospitalizados randomizados a recibir 1. Cis(Z)-zuclopenthixol: dose 40 mg/day. N = 30 o bien 2. Haloperidol: dose 10 mg/day. N = 33. Se evaluaron los desenlaces incluidos en el perfil de evidencia entre ellos incluidos el estado mental global (continuo o dicotomico (desenlace critico) y eventos adversos (desenlaces importantes) que incluyeron movimientos anormales, akatisia y uso de medicacion de rescate. Existe incertidumbre sobre el efecto del zuclopenthixol frente a haloperidol en los scores globales de estado mental, el zuclopenthixol no podria no asociarse con eventos adversos evaluados. Estos resultados estan basados en una muy baja certeza de la evidencia por alto riesgo de sesgo (attrition bias, datos de resultados incomplete, sesgo de seleccion de Berkson y sesgo diagnostic). CONCLUSIONES: ¿Deberia usarse Zuclopenthixol frente a Haloperidol para el tratamiento de los episódios psicóticos agudos? Certeza de la evidencia: Muy baja.

Can typical and atypical antipsychotics show differential effectiveness in treating paranoia and hallucinations in schizophrenia?

A dopamine excess is thought to be involved in positive psychotic symptoms in schizophrenia. All current antipsychotics show a degree of dopamine receptor antagonism. Little is known about the differential effectiveness of different antipsychotics in treating specific sets of symptoms. We report the case of a 35-year-old man with schizophrenia who presented with prominent hallucinatory symptoms (Positive and Negative Syndrome Scale [PANSS] P1=5, P3=5, P6=5) resistant to high doses of a dopamine, serotonin receptor antagonist, olanzapine. Switching from olanzapine to zuclopenthixol, a dopamine D2 receptor antagonist, led to a complete shift of his symptomatology: his hallucinations abated, however, he presented as very highly paranoid (PANSS P1=6, P3=2, P6=7). On a combination of both antipsychotics, his symptoms subsided (PANSS P1=3, P3=2, P6=2). We discuss the potential for differential effectiveness of different antipsychotic medications in treating hallucinations and paranoia. We argue that future studies could address this question by stratifying patients based on symptoms.

Paliperidone Palmitate-Induced Delirium in an Adolescent with Schizophrenia: Case report.

Schizophrenia is a serious long-term mental disorder which usually presents in adolescence or early adulthood. However, poor adherence to oral antipsychotics can lead to relapse and rehospitalisation. We report an adolescent male with schizophrenia who was referred to the South London & Maudsley National Health Service Foundation Trust, London, UK, in 2015 due to worsening psychotic symptoms. Following poor compliance with oral medications, a four-week regimen of paliperidone palmitate long-acting injections was initiated, with an initial positive response. However, 10 days after the second dose, the patient developed severe acute-onset delirium with fluctuating levels of consciousness. Paliperidone palmitate was discontinued and the patient instead underwent a course of zuclopenthixol decanoate long-acting injections with a favourable outcome.

Zuclopenthixol dihydrochloride for schizophrenia.

BACKGROUND: Oral zuclopenthixol dihydrochloride (Clopixol) is an anti-psychotic treatment for people with psychotic symptoms, especially those with schizophrenia. It is associated with neuroleptic malignant syndrome, a prolongation of the QTc interval, extra-pyramidal reactions, venous thromboembolism and may modify insulin and glucose responses. OBJECTIVES: To determine the effects of zuclopenthixol dihydrochloride for treatment of schizophrenia. SEARCH METHODS: We searched the Cochrane Schizophrenia Group's Trials Register (latest search 09 June 2015). There were no language, date, document type, or publication status limitations for inclusion of records in the register. SELECTION CRITERIA: All randomised controlled trials (RCTs) focusing on zuclopenthixol dihydrochloride for schizophrenia. We included trials meeting our inclusion criteria and reporting useable data. DATA COLLECTION AND ANALYSIS: We extracted data independently. For binary outcomes, we calculated risk ratio (RR) and its 95% confidence interval (CI), on an intention-to-treat basis. For continuous data, we estimated the mean difference (MD) between groups and its 95% CI. We employed a random-effect model for analyses. We assessed risk of bias for included studies and created 'Summary of findings' tables using GRADE. MAIN RESULTS: We included 20 trials, randomising 1850 participants. Data were reported for 12 comparisons, predominantly for the short term (up to 12 weeks) and inpatient populations. Overall risk of bias for included studies was low to unclear.Data were unavailable for many of our pre-stated outcomes of interest. No data were available, across all comparisons, for death, duration of stay in hospital and general functioning.Zuclopenthixol dihydrochloride versus: 1. placeboMovement disorders (EPSEs) were similar between groups (1 RCT, n = 28, RR 6.07 95% CI 0.86 to 43.04 very low-quality evidence). There was no clear difference in numbers leaving the study early (2 RCTs, n = 100, RR 0.29, 95% CI 0.01 to 6.60, very low-quality evidence). 2. chlorpromazineNo clear differences were found for the outcomes of global state (average CGI-SI endpoint score) (1 RCT, n = 60, MD 0.00, 95% CI -0.49 to 0.49) or movement disorders (EPSEs) (3 RCTs, n = 199, RR 0.94, 95% CI 0.61 to 1.45), both very low-quality evidence. More people left the study early for any reason from the zuclopenthixol group (6 RCTs, n = 766, RR 0.54, 95% CI 0.36 to 0.81, low-quality evidence). 3. chlorprothixeneThere was no clear difference in numbers leaving the study early for any reason (1 RCT, n = 20, RR 1.00, 95% CI 0.34 to 2.93, very low-quality evidence). 4. clozapineNo useable data were presented. 5. haloperidolNo clear differences between treatment groups were found for the outcomes global state score (average CGI endpoint score) (1 RCT, n = 49, MD 0.13, 95% CI -0.30 to 0.55) or leaving the study early (2 RCTs, n = 141, RR 0.99, 95% CI 0.72 to 1.35), both very low-quality evidence. 6. perphenazineThose receiving zuclopenthixol were more likely to require medication in the short term for EPSEs than perphenazine (1 RCT, n = 50, RR 1.90, 95% CI 1.12 to 3.22, very low-quality evidence). Similar numbers left the study early (2 RCTs, n = 104, RR 0.63, 95% CI 0.27 to 1.47, very low-quality evidence). 7. risperidoneThose receiving zuclopenthixol were more likely to require medications for EPSEs than risperidone (1 RCT, n = 98,RR 1.92, 95% CI 1.12 to 3.28, very low quality evidence). There was no clear difference in numbers leaving the study early ( 3 RCTs, n = 154, RR 1.30, 95% CI 0.84 to 2.02) or in mental state (average PANSS total endpoint score) (1 RCT, n = 25, MD -3.20, 95% CI -7.71 to 1.31), both very low-quality evidence). 8. sulpirideNo clear differences were found for global state (average CGI endpoint score) ( 1 RCT, n = 61, RR 1.18, 95% CI 0.49 to 2.85, very low-quality evidence), requiring hypnotics/sedatives (1 RCT, n = 61, RR 0.60, 95% CI 0.27 to 1.32, very low-quality evidence) or leaving the study early (1 RCT, n = 61, RR 2.07 95% CI 0.97 to 4.40, very low-quality evidence). 9. thiothixeneNo clear differences were found for the outcomes of 'global state (average CGI endpoint score) (1 RCT, n = 20, RR 0.50, 95% CI 0.17 to 1.46) or leaving the study early (1 RCT, n = 20, RR 0.57, 95% CI 0.24 to 1.35), both very low-quality evidence). 10. trifluoperazineNo useable data were presented. 11. zuclopenthixol depotThere was no clear difference in numbers leaving the study early (1 RCT, n = 46, RR 1.95, 95% CI 0.36 to 10.58, very low-quality evidence). 12. Zuclopenthixol dihydrochloride (cis z isomer) versus zuclopenthixol (cis z/trans e isomer)There were no clear differences in reported side-effects ( 1 RCT, n = 57, RR 1.34, 95% CI 0.82 to 2.18, very low-quality evidence) and in numbers leaving the study early (4 RCTs, n = 140, RR 2.15, 95% CI 0.49 to 9.41, very low-quality evidence). AUTHORS' CONCLUSIONS: Zuclopenthixol dihydrochloride appears to cause more EPSEs than clozapine, risperidone or perphenazine, but there was no difference in EPSEs when compared to placebo or chlorpromazine. Similar numbers required hypnotics/sedatives when zuclopenthixol dihydrochloride was compared to sulpiride, and similar numbers of reported side-effects were found when its isomers were compared. The other comparisons did not report adverse-effect data.Reported data indicate zuclopenthixol dihydrochloride demonstrates no difference in mental or global states compared to placebo, chlorpromazine, chlorprothixene, clozapine, haloperidol, perphenazine, sulpiride, thiothixene, trifluoperazine, depot and isomers. Zuclopenthixol dihydrochloride, when compared with risperidone, is favoured when assessed using the PANSS in the short term, but not in the medium term.The data extracted from the included studies are mostly equivocal, and very low to low quality, making it difficult to draw firm conclusions. Prescribing practice is unlikely to change based on this meta-analysis. Recommending any particular course of action about side-effect medication other than monitoring, using rating scales and clinical assessment, and prescriptions on a case-by-case basis, is also not possible.There is a need for further studies covering this topic with more antipsychotic comparisons for currently relevant outcomes.

Frontal D2/3 Receptor Availability in Schizophrenia Patients Before and After Their First Antipsychotic Treatment: Relation to Cognitive Functions and Psychopathology.

BACKGROUND: We have previously reported associations between frontal D2/3 receptor binding potential positive symptoms and cognitive deficits in antipsychotic-naïve schizophrenia patients. Here, we examined the effect of dopamine D2/3 receptor blockade on cognition. Additionally, we explored the relation between frontal D2/3 receptor availability and treatment effect on positive symptoms. METHODS: Twenty-five antipsychotic-naïve first-episode schizophrenia patients were examined with the Positive and Negative Syndrome Scale, tested with the cognitive test battery Cambridge Neuropsychological Test Automated Battery, scanned with single-photon emission computerized tomography using the dopamine D2/3 receptor ligand [(123)I]epidepride, and scanned with MRI. After 3 months of treatment with either risperidone (n=13) or zuclopenthixol (n=9), 22 patients were reexamined. RESULTS: Blockade of extrastriatal dopamine D2/3 receptors was correlated with decreased attentional focus (r = -0.615, P=.003) and planning time (r = -0.436, P=.048). Moreover, baseline frontal dopamine D2/3 binding potential and positive symptom reduction correlated positively (D2/3 receptor binding potential left frontal cortex rho = 0.56, P=.003; D2/3 receptor binding potential right frontal cortex rho = 0.48, P=.016). CONCLUSIONS: Our data support the hypothesis of a negative influence of D2/3 receptor blockade on specific cognitive functions in schizophrenia. This is highly clinically relevant given the well-established association between severity of cognitive disturbances and a poor functional outcome in schizophrenia. Additionally, the findings support associations between frontal D2/3 receptor binding potential at baseline and the effect of antipsychotic treatment on positive symptoms.

Higher serum concentrations of tyrosine and glutamate in schizophrenia patients treated with clozapine, compared to in those treated with conventional antipsychotics.

RATIONALE: The effect of long-term treatment with the atypical antipsychotic clozapine on the serum amino acid profile in schizophrenia patients has not previously been studied. OBJECTIVES: The aim of this study was to compare serum amino acid patterns in patients on long-term clozapine treatment with long-term conventional antipsychotic treatment, and their relationships to insulin resistance and antipsychotic serum concentrations. METHODS: Thirty-three patients with schizophrenia or schizoaffective disorder on long-term treatment (mean 8.3 years) with clozapine (n=20) or conventional antipsychotics (n=13) were studied. Amino acids were quantified in fasting serum samples by ion exchange chromatography and markers of insulin resistance and antipsychotic drug concentrations were determined by standard methods. RESULTS: Several amino acids, most notably tyrosine and glutamic acid, were elevated above the reference range in several patients receiving clozapine. Additionally, significantly higher mean values of tyrosine (1.5-fold, p=0.001), glutamic acid (2-fold, p=0.0005) and six other amino acids were observed in the clozapine group than in the conventional antipsychotic group. Several amino acids were related to insulin resistance in both treatment groups. CONCLUSIONS: In this study, we show that serum tyrosine and glutamic acid concentrations are markedly elevated in patients on long-term clozapine treatment, compared to patients on long-term conventional antipsychotic treatment. These findings are of importance since these two amino acids have been implicated in the pathophysiology of schizophrenia.

Zuclopenthixol versus placebo for schizophrenia.

BACKGROUND: Zuclopenthixol is an older antipsychotic that has three distinct formulations (zuclopenthixol dihydrochloride, zuclopenthixol acetate or Acuphase and zuclopenthixol decanoate). Although it has been in common use for many years no previous systematic review of its efficacy compared to placebo in schizophrenia has been undertaken. OBJECTIVES: To evaluate the effectiveness of all formulations of zuclopenthixol when compared with a placebo in schizophrenia. SEARCH METHODS: On 6 November 2013 and 20 October 2015, we searched the Cochrane Schizophrenia Group Trials Register, which is based on regular searches of MEDLINE, EMBASE, CINAHL, BIOSIS, AMED, PubMed, PsycINFO, and registries of clinical trials. We also checked the references of all included studies and contacted authors of included studies for relevant studies and data. SELECTION CRITERIA: We included all randomised controlled trials comparing zuclopenthixol of any form with placebo for treatment of schizophrenia or schizophrenia-like psychoses. DATA COLLECTION AND ANALYSIS: We extracted and cross-checked data independently. We identified only a small number of studies so we cross checked all studies. We calculated fixed-effect relative risks (RR) and 95% confidence intervals (CI) for dichotomous data. We analysed by intention-to-treat. Where possible we converted continuous outcomes into dichotomous outcomes. When this was not possible we used mean differences (MD) for continuous variables. We assessed risk of bias for included studies and used GRADE (Grading of Recommendations Assessment, Development and Evaluation) to create a 'Summary of findings' table. MAIN RESULTS: Only two studies, with a total of 65 participants, were eligible for inclusion in the review. Overall the quality of the two studies was low, with small study populations and significant sources of bias, so we were not able to use all the data in our comparisons. . The studies were old from 1968 and 1972, and would be unlikely to pass modern peer review standard. We were only able to find short-term data and only trials randomising zuclopenthixol dihydrochloride. We also hoped to identify data for zuclopenthixol acetate versus placebo and zuclopenthixol decanoate versus placebo comparisons. We were unable to identify any studies that included data on these two fairly widely used drugs.For our primary outcome of interest, clinically significant improvement, we found one study that provided useable data. Global state measured by clinical global impression scale (CGI) improvement showed different ratings when assessed by a psychiatrist or a nurse.The psychiatrist scores failed to achieve statistical significance, however when assessed by nursing staff, the difference favouring zuclopenthixol did reach statistical significance (1 RCT n = 29, RR 2.57 95% CI 1.06 to 6.20, very low quality data). There was also evidence of increased sedation with those treated with zuclopenthixol when compared with placebo (1 RCT n = 29, RR 4.67 95% CI 1.23 to 17.68, very low quality data). 'Leaving the study early' data were equivocal. No useable data were available for outcomes such as relapse, mental state, death, quality of life, service use or economic costs. AUTHORS' CONCLUSIONS: For people with schizophrenia this review shows that zuclopenthixol dihydrochloride may help with the symptoms of schizophrenia. The review provides some trial evidence that, if taking zuclopenthixol dihydrochloride, people may experience some adverse effects and sedation compared with placebo. However this evidence is of very low quality and with some significant sources of bias. There are no data for zuclopenthixol decanoate or zuclopenthixol acetate.For clinicians, the available trial data on the absolute effectiveness of zuclopenthixol dihydrochloride do support its use but the limited nature of the data and significant sources of bias make conclusions hard to draw. Zuclopenthixol in all three forms is a commonly used antipsychotic and it is disappointing that there are so few data regarding its use.

Treatment of aggressive behavior problems in boys with intellectual disabilities using zuclopenthixol.

OBJECTIVE: Disruptive or challenging behavior problems pose a threat to children and adolescents with intellectual disabilities and their caregivers. Psychopharmacological treatment is mostly studied with new-generation antipsychotics and has been criticized for adverse side effects. This study examined the effect of the classic antipsychotic zuclopenthixol. METHODS: A total of 39 boys (ages 8.0-17.11 years) with learning disabilities were included and examined for a response to zuclopenthixol during a 6 week period of open label treatment. Doses started low and were adapted individually. From responders, zuclopenthixol was randomly withdrawn for 12 weeks. Responses to withdrawal were observed by external raters using the Modified Overt Aggression Scale. RESULTS: Of all patients included into the study, 15 were not randomized because of insufficient therapeutic effect, adverse event, or noncompliance. Kaplan-Meier estimations showed less aggressive behavior problems for the continuing subgroup (n=9) than in the placebo group (n=15). Individual doses stayed <10 mg/day. CONCLUSIONS: Zuclopenthixol proved to be effective in reducing challenging behavior in boys even at low doses.

[Emergency psychopharmacotherapy in Hungary -- preliminary data]. / Sürgosségi pszichofarmakoterápia Magyarországon -- elozetes adatok.

OBJECTIVES: Although the number of patients admitted for psychiatric emergency care is increasing according to data from various countries, there are no large-scale studies assessing clinical emergency practice and in several countries no national guidelines have been published concerning emergency care in psychiatry. The aim of our study was to assess practice related to emergency care of agitated-psychotic patients in Hungary. METHODS: Anonymous survey questionnaire with questions related to care of an agitated patient showing psychotic symptoms was dispatched to 210 institutions providing psychiatric care in Hungary in 2013. RESULTS: The overwhelming majority of the 155 participating clinicians would use haloperidol (92.9%) and benzodiazepines (81.3%), 74.8% in a dual combination. 18.7% would apply monotherapy and 5.2% a triple combination of medications. 59.4% would use i.v. and 23.9% i.m. therapy, and 9% would apply the combination of these two. In case of failure of first-line therapy, 76.8% of participants would repeat the previous medication. CONCLUSIONS: The aim of our study was to assess emergency interventions in psychiatry focusing on different psychopharmacological approaches. Our results provide a cross-sectional view on current practice in Hungary, and therefore may contribute to outlining practice-coherent guidelines and also provide the opportunity for a comparison with international trends.

Therapeutic drug monitoring of zuclopenthixol in a double-blind placebo-controlled discontinuation study in adults with intellectual disabilities and aggressive behaviour.

The trial was a double-blind, placebo-controlled comparison with a discontinuation design. 49 mentally retarded patients with aggressive behaviour were treated with zuclopenthixol at a dose of 2-20 mg/d. At each visit the clinical effect was evaluated. Correlations between dose, serum concentration, and efficacy measures were calculated. The mean dose was 10.0 mg/day (±5.17); the mean serum concentration 4.19 ng/mL (±3.16). Associations of dosage, serum concentration and clinical efficiency did not result in coherent patterns. Correlations with clinical efficiency measures appeared to be contradictory for dosage and serum concentrations, respectively. As no consistent associations between dosage, serum concentration, and clinical efficiency measures were found, different hypotheses explaining the results are discussed.

Zuclopenthixol decanoate in pregnancy: successful outcomes in two consecutive offsprings of the same mother.

INTRODUCTION: Almost all individual antipsychotics are classified into the intermediate pregnancy risk category as no or limited data exist about human pregnancy outcomes. We presented the case of zuclopenthixol decanoate using in two successive pregnancies of the same woman, which had not been published in the available peer-reviewed literature. CASE REPORT: A middle-age female subject who suffered from schizophrenia received zuclopenthixol decanoate injection during her two consecutive pregnancies. About four and a half months before diagnosis of the first pregnancy (to approximately 3.5 years after psychosis emergence), zuclopenthixol decanoate (400 mg every other week, im injection) was introduced to the treatment protocol (due to previous non-compliance with haloperidol and risperidone). A significant clinical improvement was achieved and the dose during pregnancy was reduced to 200 mg once monthly and maintained to date. In both pregnancies the women gave birth to healthy girls who have been developing normally until now, at their ages of 6 months and of 3.5 years. During pregnancy and after giving birth to children the mothers' psychiatric status and her social functioning were significantly improved and are still stable. Close monitoring of the mother's health, a multidisciplinary approach to both her treatment and the monitoring of pregnancies as well as the complete compliance with the prescribed drug protocol were likely to be crucial for the therapeutic success. CONCLUSION: A favorable outcome of the present case suggests that the zuclopenthixol decanoate is a rational therapeutic option for pregnant women suffering from psychosis when the expected benefit exceed the potential risk, but a definitive evidence for its safety requires large, controlled studies.

[Mineralization of the basal ganglia as the supposed cause of poor tolerance of zuclopenthixol in a patient with long-term untreated paranoid schizophrenia]. / Mineralizacja jader podstawy jako domniemana przyczyna zlej tolerancji zuklopentyksolu u chorej z wieloletnia nieleczona schizofrenia paranoidalna.

Formations described as intracranial calcifications can appear in the course of diseases of the central nervous system, other systems and organs (e.g. endocrine), but also as a disorder of idiopathic character. They are frequently located in subcortical nuclei and usually constitute an incidental finding. This report presents the case of a patient suffering from paranoid schizophrenia for approximately 40 years, who did not agree to any treatment and was hospitalized against her will because she was the threat to the lives of others. She was treated with zuklopentixol resulting in positive symptoms reduction and considerable improvement in social functioning. Unfortunately neurological symptoms appeared: bradykinesis, rigidity--of the type of the lead pipe, balance, posture and gait abnormalities, disturbances in precise hands movements, double-sided Rossolimo's sign, plantar reflex without the participation of the big toe on the left. Neuroimaging studies have demonstrated changes in the form of lenticular nuclei calcification and reduction of signal intensity in posterior parts of both putamens. Neurological symptoms decreased significantly after switching to atypical neuroleptic (olanzapine), and the patient did not require any additional treatment. Mineralization of the basal ganglia can often be associated with psychiatric disorders and it shouldn't be neglected because it can require modification of pharmacotherapy or additional neurological treatment.

Network-assisted investigation of antipsychotic drugs and their targets.

Antipsychotic drugs are tranquilizing psychiatric medications primarily used in the treatment of schizophrenia and similar severe mental disorders. So far, most of these drugs have been discovered without knowing much on the molecular mechanisms of their actions. The available large amount of pharmacogenetics, pharmacometabolomics, and pharmacoproteomics data for many drugs makes it possible to systematically explore the molecular mechanisms underlying drug actions. In this study, we applied a unique network-based approach to investigate antipsychotic drugs and their targets. We first retrieved 43 antipsychotic drugs, 42 unique target genes, and 46 adverse drug interactions from the DrugBank database and then generated a drug-gene network and a drug-drug interaction network. Through drug-gene network analysis, we found that seven atypical antipsychotic drugs tended to form two clusters that could be defined by drugs with different target receptor profiles. In the drug-drug interaction network, we found that three drugs (zuclopenthixol, ziprasidone, and thiothixene) tended to have more adverse drug interactions than others, while clozapine had fewer adverse drug interactions. This investigation indicated that these antipsychotics might have different molecular mechanisms underlying the drug actions. This pilot network-assisted investigation of antipsychotics demonstrates that network-based analysis is useful for uncovering the molecular actions of antipsychotics.

Zuclopenthixol acetate for acute schizophrenia and similar serious mental illnesses.

BACKGROUND: Medication used for acute aggression in psychiatry must have rapid onset of effect, low frequency of administration and low levels of adverse effects. Zuclopenthixol acetate is said to have these properties. OBJECTIVES: To estimate the clinical effects of zuclopenthixol acetate for the management of acute aggression or violence thought to be due to serious mental illnesses, in comparison to other drugs used to treat similar conditions. SEARCH METHODS: We searched the Cochrane Schizophrenia's Group Trials Register (July 2011). We supplemented this by citation searching and personal contact with authors and relevant pharmaceutical companies. SELECTION CRITERIA: All randomised clinical trials involving people thought to have serious mental illnesses comparing zuclopenthixol acetate with other drugs. DATA COLLECTION AND ANALYSIS: Two review authors extracted and cross-checked data independently. We calculated fixed-effect relative risks (RR) and 95% confidence intervals (CI) for dichotomous data. We analysed by intention-to-treat. We used mean differences (MD) for continuous variables. MAIN RESULTS: We found no data for the primary outcome, tranquillisation. Compared with haloperidol, zuclopenthixol acetate was no more sedating at two hours (n = 40, 1 RCT, RR 0.60, 95% CI 0.27 to 1.34). People given zuclopenthixol acetate were not at reduced risk of being given supplementary antipsychotics (n = 134, 3 RCTs, RR 1.49, 95% CI 0.97 to 2.30) although additional use of benzodiazepines was less (n = 50, 1 RCT, RR 0.03, 95% CI 0.00 to 0.47). People given zuclopenthixol acetate had fewer injections over seven days compared with those allocated to haloperidol IM (n = 70, 1 RCT, RR 0.39, 95% CI 0.18 to 0.84, NNT 4, CI 3 to 14). We found no data on more episodes of aggression or harm to self or others. One trial (n = 148) reported no significant difference in adverse effects for people receiving zuclopenthixol acetate compared with those allocated haloperidol at one, three and six days (RR 0.74, 95% CI 0.43 to 1.27). Compared with haloperidol or clotiapine, people allocated zuclopenthixol did not seem to be at more risk of a range of movement disorders (< 20%). Three studies found no difference in the proportion of people getting blurred vision/dry mouth (n = 192, 2 RCTs, RR at 24 hours 0.90, 95% CI 0.48 to 1.70). Similarly, dizziness was equally infrequent for those allocated zuclopenthixol acetate compared with haloperidol (n = 192, 2 RCTs, RR at 24 hours 1.15, 95% CI 0.46 to 2.88). There was no difference between treatments for leaving the study before completion (n = 522, RR 0.85, 95% CI 0.31 to 2.31). One study reported no difference in adverse effects and outcome scores, when high dose (50-100 mg/injection) zuclopenthixol acetate was compared with low dose (25-50 mg/injection) zuclopenthixol acetate. AUTHORS' CONCLUSIONS: Recommendations on the use of zuclopenthixol acetate for the management of psychiatric emergencies in preference to 'standard' treatment have to be viewed with caution. Most of the small trials present important methodological flaws and findings are poorly reported. This review did not find any suggestion that zuclopenthixol acetate is more or less effective in controlling aggressive acute psychosis, or in preventing adverse effects than intramuscular haloperidol, and neither seemed to have a rapid onset of action. Use of zuclopenthixol acetate may result in less numerous coercive injections and low doses of the drug may be as effective as higher doses. Well-conducted pragmatic randomised controlled trials are needed.

Effects of zuclopenthixol on aggressive disruptive behavior in adults with mental retardation--a 2-year follow-up on a withdrawal study.

INTRODUCTION: People with mental retardation often display aggressive behavior against themselves or others making care within institutions or foster families difficult. Due to a lack of viable alternatives, antipsychotics of the first and second generations are often used for long-term treatment despite the fact that only data about short-term treatment exist. METHODS: A short-time withdrawal trial of 12 weeks (n = 39) was extended at open label to 2 years. 31 patients received zuclopenthixol after the end of the withdrawal and were examined using the same instruments as in the withdrawal period (DAS, MOAS, CGI). RESULTS: Patients still treated with zuclopenthixol after 2 years (n = 21) benefitted, compared to the drop-outs (n = 10). Analyses of time trends revealed an early effect of zuclopenthixol which could not be enhanced afterwards. DISCUSSION: Zuclopenthixol proved to be safe and effective to keep a lower rate of aggressive behavior in adults with mental retardation also over a longer period of time.